Analysis of data from multiclinic trials.

Because the clinics in a multiclinic randomized clinical trial represent neither fixed stratification effects nor random classificatory effects, the appropriate analysis of data from such a trial has been the subject of controversy and debate. The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed. Is it ever valid to ignore the effects of clinics in the analysis? Is it ever valid to drop clinics from the analysis? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor? Assuming that clinics will be taken account of in the analysis, should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments? How should the data be analyzed if there is evidence of treatment-by-clinic interaction?

[1]  A. B. Hill.  Statistical Methods in Clinical and Preventive Medicine , 1962 .

[2]  R. McHugh,et al.  NON-ORTHOGONALITY IN THE TWO-WAY CLASSIFICATION FOR THE MIXED EFFECTS FINITE POPULATION MODEL. , 1965, Biometrics.

[3]  Frank Yates,et al.  The Analysis of Multiple Classifications with Unequal Numbers in the Different Classes , 1934 .

[4]  M. Buyse,et al.  Quality of institutional participation in multicenter clinical trials. , 1981, The New England journal of medicine.

[5]  David R. Cox.  Planning of Experiments , 1958 .

[6]  J. Fleiss.  Multicentre clinical trials: Bradford Hill's contributions and some subsequent developments. , 1982, Statistics in Medicine.

[7]  D. Weiss,et al.  Planning multicenter clinical trials: a biostatistician's perspective. , 1983, Controlled clinical trials.

[8]  J. Grizzle,et al.  A note on stratifying versus complete random assignment in clinical trials. , 1982, Controlled clinical trials.

[9]  J. Grizzle,et al.  Analysis of data from multiclinic experiments. , 1975, Biometrics.

[10]  S. Lagakos,et al.  Practical experience of randomization in cancer trials: an international survey. , 1982, British Journal of Cancer.

[11]  J. Fleiss.  The design and analysis of clinical experiments , 1987 .

[12]  D. DeMets,et al.  Fundamentals of Clinical Trials , 1982 .

[13]  J. Stjernswärd,et al.  The Conduct of a Cooperative Clinical Trial , 1981, Recent Results in Cancer Research.

[14]  R. McHugh,et al.  Post-stratification in the randomized clinical trial. , 1983, Biometrics.

[15]  Bernard G. Greenberg,et al.  Conduct of Cooperative Field and Clinical Trials , 1959 .

[16]  S. Pocock,et al.  Clinical Trials: A Practical Approach , 1984 .

[17]  N. Lange,et al.  A computerized patient registration and treatment randomization system for multi-institutional clinical trials. , 1985, Controlled clinical trials.